Project Summary The sense of touch enables everyday human behaviors, including feeding, navigation and social interaction. The goal of this research is to define the peripheral mechanisms that encode touch in mammals. This project focuses on Merkel cell-neurite complexes, which are gentle-touch receptors found in body sites specialized for fine touch. Mechanosensitive Merkel cells form synaptic-like contacts with fast-conducting afferents of dorsal root ganglia. Merkel cells are proposed to activate sensory afferents by neurotransmitter release at conventional chemical synapses, however, the molecular mechanisms of neurotransmission remain unknown. This application?s central hypothesis is that Merkel cells employ SNARE-dependent vesicular release of monoaminergic neurotransmitters to activate firing in sensory afferents. The hypothesis will be tested using a combination of live-cell imaging, transgenic mouse models, ex vivo electrophysiology, pharmacology, and sensory behavioral tests. Aim 1 will test if Merkel cells employ SNARE-mediated vesicle release of neurotransmitter. Aim 2 will determine whether Merkel cells employ monoaminergic neurotransmission to excite firing in tactile afferents. Aim 3 will elucidate if monoaminergic neurotransmission is required for gentle-touch evoked behaviors. The proposed studies will define the molecular mechanisms of synaptic transmission and post-synaptic receptor pathways at the Merkel cell-neurite complex. This knowledge will our understanding of the fundamental principles that govern tactile function and encoding in the healthy nervous system.